The availability of structurally well-defined synthetic antigens permitted the elucidaton of many aspects of the molecular and cellular basis of antigenicity as well as of other immunological phenomena. The present proposal is devoted mainly to problems of paramount importance for a better grasp of immunological phenomena; genetic control of immune response, cell to cell cooperation, mechanisms involved in B cell activation, and autoimmunity. Significant progress in elucidating the mechanisms responsible for generating genetic variations in the immune system was made by studying the genetic control of responses to synthetic antigens. The use of ordered peptides of known sequences opens the way for a better understanding of the molecular nature of genetic defects. The development of antigen specific T cell factors permit to test directly the role of T and B cells in genetically regulated immune responses and the mechanism of cell to cell cooperation. The objectives of the proposed research are: to continue to analyse the genetic control of immune response at the molecular and cellular levels, using synthetic polypeptides including ordered peptides as well as T independent immunogens, to elucidate the mechanism(s) by which immune response genes are operating and to establish the role of the different cell types in the immune response as a function of the antigen structure and the genetic constitution of the animal. In recent years we have become interested in the genetic regulation and cellular basis of the immune response to collagen and nucleic acids. Both these types of molecules have unique structural features on the one hand, and they are known to be involved in some immunological disorders, e.g. autoimmune diseases on the other hand. BIBLIOGRAPHIC REFERENCES: G.E. Matthyssens, E. Hurwitz, D. Givol and M. Sela. Binding of histamine- and other ligand-conjugated macromolecules to lymphocytes. Molecular and Cellular Biochemistry 7, 119 (1975). M. Sela and E. Mozes. The role of antigenic structure in B lymphocyte activation. Transplantation Reviews 23, 189 (1975).